Melanoma is a type of skin cancer whose incidence has steadily risen particularly in the Caucasian[unreadable] population over the last few decades. In the advanced stages of the disease, melanomas are characterized[unreadable] with a high metastatic potential, are extremely refractory to adjuvant therapies like radio- or chemotherapy[unreadable] and are often fatal. These observations underscore the need for developing novel markers indicative of[unreadable] metastatic potential and improved treatment modalities targeting the metastatic component of the disease.[unreadable] Melanoma differentiation associated gene-9 (mda-9), also known as syntenin, is an adapter molecule that[unreadable] plays important roles in diverse cell signaling mechanisms. Recent experiments document an association of[unreadable] mda-9/syntenin with metastatic cancers. A gradual increase in mda-9/syntenin expression level was[unreadable] observed with the progression of melanomas and overexpression of mda-9/syntenin in poorly metastatic[unreadable] breast or gastric cancer cells increased their invasion and migration properties. Inhibition of mda-9/syntenin[unreadable] by siRNA suppressed the invasive phenotype of aggressive melanoma cells indicating that mda-9/syntenin[unreadable] might play a key role in mediating the metastatic process. Based on these findings, the studies in this[unreadable] proposal will determine the significance of mda-9/syntenin in melanoma progression through the following[unreadable] specific aims: i) To correlate changes in mda-9/syntenin expression with different stages of human[unreadable] melanoma, ii) To analyze the effect of overexpresssion of mda-9/syntenin on poorly metastatic melanomas[unreadable] and iii) To target mda-9/syntenin as a potential therapeutic intervention for metastatic melanomas.[unreadable] Successful completion of these studies will facilitate the understanding of mda-9/syntenin in melanoma[unreadable] metastasis and its development as a diagnostic and/or prognostic tool and a therapeutic target for metastatic[unreadable] melanomas.Dr. Sarkar qualifies as Category #1 in the Guidelines as a New Investigator with extensive[unreadable] expertise in melanoma biology. This P&F study will utilize the services of Cores A, B, C, and D.